Quantitative estimation of thrombus volume and density using micro-computed tomography in patients with ST-elevation myocardial infarction, who undergo primary percutaneous coronary intervention and thrombus aspiration

Background: The presence of large thrombus burden in patients with STEMI has been recognized as an independent risk factor for major adverse cardiovascular events. The prognostic significance of initial angiographic thrombus burden and post-aspiration residual thrombus burden have already been investigated. However, evidence on the qualitative and quantitative evaluation of aspirated thrombus characteristics, as well as their association with post-primary PCI angiographic outcomes is lacking. Purpose-Methods: The main objective of this study was to develop a methodology for the quantification of extracted thrombotic material through accurate measurement of the volume, surface and density of aspirated thrombus via micro-Computed Tomography in patients with STEMI, in whom primary PCI is performed. Secondary endpoints of the study were the correlation of thrombus volume, surface and density, as quantified by microtomography, with clinical, electrocardiographic and angiographic outcomes. Furthermore, the aforementioned methodology was applied in a study population subset for two additional purposes: i) to investigate the safety and feasibility of using guide extension catheters for thrombus aspiration ii) to identify correlations between the derived volumetric findings with levels of serum ceramides.Results: We enrolled 113 consecutive patients with STEMI undergoing primary PCI and thrombus aspiration. Microtomography effectively quantified the volume, the surface and the density of all aspirated thrombi. No sample disintegration was observed and all thrombi were suitable for micro-CT scanning. Aspirated volume and surface were significantly higher in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were: vessel diameter, right coronary artery and smoking. Thrombus volume and surface were independently associated with distal embolization, no-reflow phenomenon and angiographically evident residual thrombus. Higher thrombus density was correlated with worse pre-procedural TIMI flow. Furthermore, patients with higher aspirated volume and surface developed less ST-resolution. Regarding the further applications of the developed methodology: i) among 11 patients with large thrombotic burden, to whom guide extension catheters were applied for thrombus aspiration, no adverse angiographic outcomes occurred, with the exception of 1 distal embolization. In 72.7% of these patients additional thrombotic material was extracted, while no major adverse cardiovascular events were observed. ii) among 38 patients, reporting at least 8 hours fasting, higher ceramide C16:0 levels were significantly, but weakly, correlated with larger aspirated thrombus volume, while C16:0, C24:0 and C24:1 were also significantly associated with larger intracoronary TB. Conclusions: Microtomography is a robust imaging technique, which allows accurate and reproducible analysis of thrombotic material. Patients with larger extracted thrombus, were more likely to experience angiographic outcomes linked with poor prognosis. Hence, despite retrievieng higher thrombotic load in these patients, current thrombectomy devices do not adequately deal with large thrombotic material. Large-scale studies are warranted to evaluate novel thrombectomy devices, including guide extension catheters, with the potential to improve outcomes in patients STEMI. To this end, quantification of serum ceramides might further improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice. Θεωρητικό υπόβαθρο: H παρουσία μεγάλης ποσότητας θρομβωτικού υλικού σε ασθενείς με STEMI έχει αναγνωριστεί ως ανεξάρτητος παράγοντας κινδύνου για μείζονα καρδιαγγειακά συμβάματα. Η προγνωστική σημασία του αγγειογραφικά παρατηρούμενου αρχικού θρομβωτικού φορτίου, καθώς και του υπολειπόμενου (μετά την αναρρόφηση) θρόμβου έχουν ήδη ερευνηθεί. Ωστόσο, δεν υπάρχει μέχρι σήμερα κάποια μέθοδος για την ποιοτική εκτίμηση και τον ακριβή προσδιορισμό του χαρακτηριστικών του αφαιρούμενου θρομβωτικού υλικού, ούτε στοιχεία για τη συσχέτισή του με τα αγγειογραφικά αποτελέσματα μετά την αγγειοπλαστική. Σκοπός-Μεθοδολογία της μελέτης: Κύριος στόχος της μελέτης ήταν η ανάπτυξη μιας μεθοδολογίας για τον απόλυτο προσδιορισμό του αφαιρούμενου θρομβωτικού φορτίου μέσω ακριβούς μέτρησης του μεγέθους και της πυκνότητας του αναρροφώμενου θρόμβου με τη χρήση μικροτομογραφίας σε ασθενείς με STEMI, στους οποίους διενεργείται πρωτογενής αγγειοπλαστική και θρομβοαναρρόφηση. Δευτερεύοντα καταληκτικά σημεία της μελέτης ήταν η συσχέτιση του όγκου, της επιφάνειας και της πυκνότητας του θρόμβου, που ποσοτικοποιήθηκαν μέσω της μικροτομογραφίας, με κλινικές, ηλεκτροκαρδιογραφικές και αγγειογραφικές εκβάσεις. Επιπρόσθετα, σε ένα υποσύνολο ασθενών η μεθοδολογία που αναπτύξαμε εφαρμόστηκε σε δύο περαιτέρω μελέτες, συγκεκριμένα: α) για την αξιολόγηση της ασφάλειας και της εφικτότητας μιας νέας τεχνικής θρομβοαναρρόφησης (με τη χρήση καθετήρων προέκτασης οδηγού καθετήρα αγγειοπλαστικής) και β) για τη συσχέτιση του θρομβωτικού φορτίου με τα επίπεδα κεραμιδίων ορού. Αποτελέσματα: Στη μελέτη συμπεριλήφθηκαν τελικώς 113 ασθενείς με STEMI, στους οποίους διενεργήθηκε πρωτογενής αγγειοπλαστική και θρομβοαναρρόφηση. Η μικροτομογραφία ποσοτικοποίησε αποτελεσματικά τον όγκο, την επιφάνεια και την πυκνότητα όλων των αναρροφούμενων θρόμβων, χωρίς να παρατηρηθεί αποσύνθεση κανενός δείγματος. Ο αναρροφούμενος όγκος και η επιφάνεια ήταν σημαντικά μεγαλύτεροι σε ασθενείς με υψηλότερο αγγειογραφικό φορτίο θρόμβου κατά Sianos. Aνεξάρτητοι προγνωστικοί παράγοντες για τον όγκο του αναρροφούμενου θρόμβου ήταν: η διάμετρος του ένοχου αγγείου, η δεξιά στεφανιαία αρτηρία ως ένοχο αγγείο και το κάπνισμα. Ο όγκος και η επιφάνεια του θρόμβου συσχετίστηκαν ανεξάρτητα με εμφάνιση περιφερικών εμβολών, με φαινόμενο μη-επαναρροής και με παρουσία αγγειογραφικά εμφανούς υπολειπόμενου θρόμβου. Υψηλότερη πυκνότητα θρόμβου συσχετίστηκε με χειρότερη προ της αγγειοπλαστικής ροή TIMI. Οι ασθενείς με μεγαλύτερο αναρροφούμενο όγκο και επιφάνεια εμφάνισαν μικρότερη ύφεση των ανασπάσεων του ST διαστήματος. Όσον αφορά στις περαιτέρω εφαρμογές της αναπτυχθείσας μεθοδολογίας: Α) στους 10 από τους 11 ασθενείς με μεγάλο θρομβωτικό φορτίο στους οποίους μελετήσαμε την εφαρμογή των καθετήρων προέκτασης οδηγού καθετήρα αγγειοπλαστικής ως καθετήρων θρομβοαναρρόφησης δεν παρατηρήθηκαν δυσμενείς αγγειογραφικές εκβάσεις, ενώ εμφανίστηκε μόλις 1 περιφερική εμβολή. Επίσης στο 72.7% αυτών των ασθενών αναρροφήθηκε επιπλέον θρομβωτκό υλικό, χωρίς να παρατηρηθούν μείζονα καρδιαγγειακά συμβάματα. Β) Σε 38 ασθενείς, στους οποίους μετρήθηκαν τα επίπεδα κεραμιδίων ορού, υπήρξε σημαντική, αλλά ασθενής συσχέτιση του κεραμιδίου C16:0 με τον αναρροφηθέντα όγκο θρόμβου, ενώ τα κεραμίδια C16:0, C24:0 και C24:1 συσχετίστηκαν με τον ενδοστεφανιαίο όγκου θρόμβου. Συμπεράσματα: H μικροτομογραφία επέτρεψε την ακριβή ποσοτικοποίηση του αναρροφούμενου θρόμβου. Όσο μεγαλύτερος ήταν ο αναρροφούμενος θρόμβος, τόσο πιθανότερο ήταν να εμφανίσει ο ασθενής κάποια αγγειογραφική έκβαση που συνδέεται με πτωχή πρόγνωση. Συνεπώς, παρά την αναρρόφηση μεγαλύτερου θρομβωτικού φορτίου σε αυτούς τους ασθενείς, οι τρέχουσες συσκευές θρομβεκτομής δεν αντιμετωπίζουν επαρκώς το μεγάλο θρομβωτικό υλικό. Η χρήση καθετήρων προέκτασης οδηγού καθετήρα αγγειοπλαστικής ως καθετήρων θρομβοαναρρόφησης θα μπορούσε να μελετηθεί περαιτέρω σε μεγαλύτερης κλίμακας μελέτες, ώστε να εφαρμοστούν μελλοντικά νέες τεχνικές θρομβοαναρρόφησης με στόχο τη βελτίωση των εκβάσεων των ασθενών με STEMI. Τέλος, νεώτεροι βιοδείκτες, όπως τα κεραμίδια ορού, μπορούν να χρησιμοποιηθούν για την ανίχνευση των ασθενών με μεγάλο θρομβωτικό φορτίο με στόχο την εξατομικευμένη αντιμετώπιση των ασθενών με STEMI

CRISSPAC: A web-based platform for predicting the SYNTAX Score and severity of coronary artery disease

CRISSPAC is an open-source web-based platform for the prediction of the Syntax Score and the severity of coronary artery disease (CAD) providing a variety of data analytics and machine learning solutions presented via an-easy-to-use graphical interface environment. The aim of the software is two-fold: (1) to facilitate both retrospective and prospective objectives dedicated to the diagnosis of the complexity of CAD; (2) to support open science principles through the public availability of the source code. Our envision is to promote software extensibility and utilization towards accurate diagnosis, decision-making processes and personalized patient management and counseling activities

Non-Vitamin K Oral Anticoagulants in Adults with Congenital Heart Disease: A Systematic Review

Adults with congenital heart disease (ACHD) experience more thromboembolic complications than the general population. We systematically searched and critically appraised all studies on the safety and efficacy of non-vitamin-K oral anticoagulants (NOACs) in adult patients with various forms of congenital heart disease. PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were used, with duplicate extraction of data and risk of bias assessment. The Newcastle-Ottawa quality assessment scale was used to assess study quality. Three studies fulfilled the inclusion criteria and were analyzed. The total number of participants was 766, with a total follow-up of 923 patient-years. The majority of patients (77%) received a NOAC for atrial arrhythmias, while the remainder were prescribed NOACs for secondary (19%) or primary (4%) thromboprophylaxis. The annual rate of thromboembolic and major bleeding events was low: 0.98% (95% CI: 0.51–1.86) and 1.74% (95% CI: 0.86–3.49) respectively. In Fontan patients, the annual rate of thromboembolic and major bleeding events was 3.13% (95% CI: 1.18–8.03) and 3.17% (95% CI: 0.15–41.39) respectively. NOACs appear safe and effective in ACHD without mechanical prostheses. Additional studies are, however, needed to confirm their efficacy in complex ACHD, especially those with a Fontan-type circulation

Correlation of Serum Acylcarnitines with Clinical Presentation and Severity of Coronary Artery Disease

Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p p p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence

Machine Learning Algorithm to Predict Obstructive Coronary Artery Disease: Insights from the CorLipid Trial

Developing risk assessment tools for CAD prediction remains challenging nowadays. We developed an ML predictive algorithm based on metabolic and clinical data for determining the severity of CAD, as assessed via the SYNTAX score. Analytical methods were developed to determine serum blood levels of specific ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and APOB/APOA1 ratio. Patients were grouped into: obstructive CAD (SS > 0) and non-obstructive CAD (SS = 0). A risk prediction algorithm (boosted ensemble algorithm XGBoost) was developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD. The study population comprised 958 patients (CorLipid trial (NCT04580173)), with no prior CAD, who underwent coronary angiography. Of them, 533 (55.6%) suffered ACS, 170 (17.7%) presented with NSTEMI, 222 (23.2%) with STEMI, and 141 (14.7%) with unstable angina. Of the total sample, 681 (71%) had obstructive CAD. The algorithm dataset was 73 biochemical parameters and metabolic biomarkers as well as anthropometric and medical history variables. The performance of the XGBoost algorithm had an AUC value of 0.725 (95% CI: 0.691–0.759). Thus, a ML model incorporating clinical features in addition to certain metabolic features can estimate the pre-test likelihood of obstructive CAD

Polycystic Ovary Syndrome Triggers Atrial Conduction Disorders: A Systematic Review and Meta-Analysis

Background: Polycystic ovary syndrome (PCOS) is closely related to various adverse cardiovascular manifestations and increased cardiovascular risk. However, atrial fibrillation (AF) development and atrial conduction abnormalities have not been thoroughly studied in patients with PCOS. Methods: This meta-analysis (CRD42021261375) was conducted in accordance with the PRISMA guidelines. Our aim was to investigate associations between PCOS and disorders in atrial conduction parameters linked with an increased risk for AF occurrence. Results: Five cohort studies with aggregate data on 406 adult women (229 with PCOS and 177 age-matched without PCOS) were included in this analysis. Our results showed a significantly increased mean difference in P-wave maximum duration (+7.63 ± 7.07 msec; p p = 0.03) of patients with PCOS compared to healthy women. The mean difference in P-wave minimum duration (−2.22 ± 2.68 msec; p = 0.11) did not reach the statistical threshold between the compared groups. Echocardiographic measurements of atrial electromechanical delay (AED) also indicated a statistically significant mean difference in favour of the PCOS group in all assessed parameters, except for atrial electromechanical coupling (PA) in the tricuspid annulus. Particularly, PCOS was associated with increased lateral PA, septal PA, inter- and intra-AED durations (mean difference: +17.31 ± 9.02 msec; p p p p Conclusions: PCOS is strongly associated with alterations in several electrocardiographic and echocardiographic parameters indicating abnormal atrial conduction. Therefore, PCOS could be considered as a causal or triggering factor of AF. Larger studies are needed to confirm these results and investigate direct associations between PCOS and AF

Volumetric Imaging of Lung Tissue at Micrometer Resolution: Clinical Applications of Micro-CT for the Diagnosis of Pulmonary Diseases

Micro-computed tomography (micro-CT) is a promising novel medical imaging modality that allows for non-destructive volumetric imaging of surgical tissue specimens at high spatial resolution. The aim of this study is to provide a comprehensive assessment of the clinical applications of micro-CT for the tissue-based diagnosis of lung diseases. This scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews, aiming to include every clinical study reporting on micro-CT imaging of human lung tissues. A literature search yielded 570 candidate articles, out of which 37 were finally included in the review. Of the selected studies, 9 studies explored via micro-CT imaging the morphology and anatomy of normal human lung tissue; 21 studies investigated microanatomic pulmonary alterations due to obstructive or restrictive lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis; and 7 studies examined the utility of micro-CT imaging in assessing lung cancer lesions (n = 4) or in transplantation-related pulmonary alterations (n = 3). The selected studies reported that micro-CT could successfully detect several lung diseases providing three-dimensional images of greater detail and resolution than routine optical slide microscopy, and could additionally provide valuable volumetric insight in both restrictive and obstructive lung diseases. In conclusion, micro-CT-based volumetric measurements and qualitative evaluations of pulmonary tissue structures can be utilized for the clinical management of a variety of lung diseases. With micro-CT devices becoming more accessible, the technology has the potential to establish itself as a core diagnostic imaging modality in pathology and to enable integrated histopathologic and radiologic assessment of lung cancer and other lung diseases

Serum Ceramides as Prognostic Biomarkers of Large Thrombus Burden in Patients with STEMI: A Micro-Computed Tomography Study

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629–0.946 and 0.846, 95% CI: 0.706–0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice

Serum Ceramides as Prognostic Biomarkers of Large Thrombus Burden in Patients with STEMI: A Micro-Computed Tomography Study

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629–0.946 and 0.846, 95% CI: 0.706–0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice